Toxicity of hemimethyl-substituted cucurbit[7]uril

Xue Yang; Wenxuan Zhao; Ziyi Wang; Ying Huang; Simon M Y Lee; Zhu Tao; Ruibing Wang

doi:10.1016/j.fct.2017.01.003

Toxicity of hemimethyl-substituted cucurbit[7]uril

Food Chem Toxicol. 2017 Oct;108(Pt B):510-518. doi: 10.1016/j.fct.2017.01.003. Epub 2017 Jan 9.

Authors

Xue Yang¹, Wenxuan Zhao², Ziyi Wang³, Ying Huang⁴, Simon M Y Lee¹, Zhu Tao⁵, Ruibing Wang⁶

Affiliations

¹ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China.
² State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China; Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China.
³ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China; Pharmaceutical Undergraduate Research Program, China Pharmaceutical University, Nanjing, China.
⁴ Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China.
⁵ Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China. Electronic address: gzutao@263.net.
⁶ State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, China. Electronic address: rwang@umac.mo.

PMID: 28082230
DOI: 10.1016/j.fct.2017.01.003

Abstract

Hemimethyl-substituted cucurbit[7]uril (HMeCB[7]), a derivative of cucurbit[7]uril (CB[7]) with nearly identical host-guest complexation properties to that of the parent, has significant potential in biomedical sciences due to its superior solubility in water. Its toxicity profile has been investigated in this work, including its developmental and organ-specific toxicities, with both in vivo zebrafish models and a relevant in vitro cellular model. These results demonstrated that HMeCB[7] has negligible developmental toxicity at concentrations up to 3.2 mM and very moderate cardiotoxicity and hepatotoxicity at concentrations of ≥0.8 mM, and is thus generally less toxic than the parent CB[7]. Our results suggest that HMeCB[7] may be a promising candidate of excipient in medicinal and pharmaceutical research fields.

Keywords: Hemimethyl-substituted cucurbit[7]uril; Macrocyclic molecule; Toxicity; Zebrafish.

MeSH terms

Animals
Bridged-Ring Compounds / chemistry*
Bridged-Ring Compounds / toxicity*
Cell Line
Chemical and Drug Induced Liver Injury
Embryo, Nonmammalian / drug effects
Heart / drug effects
Heart / embryology
Hepatocytes / drug effects
Humans
Imidazoles / chemistry*
Imidazoles / toxicity*
Models, Molecular
Stereoisomerism
Zebrafish / embryology

Substances

Bridged-Ring Compounds
Imidazoles
cucurbit(7)uril